Multiple sample applicator

ABSTRACT

A multisample dispenser including a first member for supporting a plurality of capillary tubes and a second member cooperating with and movably disposed with respect to said first member for carrying a like plurality of needlelike wire elements. Each of the wire elements is movably inserted inside a corresponding capillary tube to form a plurality of dispensing elements capable of simultaneously dispensing a plurality of predetermined sample quantities. The first member also includes a plurality of easily removable flexible retaining means each of which is arranged to firmly hold a capillary tube in the first member. Each wire element is coated with a relatively dense lubricant to provide a liquidtight seal between the wire element and the inner wall of the capillary tube in which the element is inserted.

United States Patent [72] lnventor Leslie D. Holybee Cupertino, Calif.

[21] Appl. No. 712,758

[22] Filed Mar. 13, 1968 [45] Patented Jan. 5, 1971 [73] Assignee Beckman Instruments, Inc.

a corporation of California [54] MULTIPLE SAMPLE APPLICATOR [56] References Cited UNITED STATES PATENTS 2,709,538 5/1955 Harrington 222/276X 3,216,616 1 1/1965 Blankenship, Jr. 222/386X Primary Examiner-Stanley 1-1. Tollberg Attorneys- Richard M. Jennings and Robert J. Steinmeyer ABSTRACT: A multisample dispenser including a first member for supporting a plurality of capillary tubes and a second member cooperating with and movably disposed with respect to said first member for carrying a like plurality of needlelike wire elements. Each of the wire elements is movablyv inserted inside a corresponding capillary tube to form a plurality of dispensing elements capable of simultaneously dispensing a plurality of predetermined sample quantities. The first member also includes a plurality of easily removable flexible retaining means each of which is arranged to firmly hold a capillary tube in the first member. Each wire element is coated with a relatively dense lubricant to provide a liquidtight seal between the wire element and the inner wall of the capillary tube in which the element is inserted.

PATENTEU JAN 5197:

SHEU 1 OF 2 INVENTOR. LESLIE D. HOLYBEE ,ATTORNEY MULTIPLE SAMPLE APPLICATOR BACKGROUND This invention relates in general to laboratory instruments for accurately handling extremely small sample quantities and more particularly to a multisample dispensing apparatus for simultaneously dispensing a plurality of predetermined sample quantities in the microliter range.

In many technical areas there is a great need for instruments capable of accurately handling microliter sample quantities. For instance, in the field of gel electrophoresis, a process used to separate chemical similar particles by virtue of their different migration velocities in the presence of an electrical field, it is frequently necessary to repeatedly deposit a plurality of minute and identical sample quantities in a supporting gel carrier medium. In the past it has been the practice to employ a conventional syringe, such as a Hamilton syringe, and apply one sample quantity at a time to the gel medium. Obviously,

not only is such a method cumbersome and time-consuming but, also, it is subject to large errors in both initial alignment of the sample in the gel medium and accurate deposition of equal sample quantity amounts, especially in microliter quantities.

This invention contemplates a multisample dispenser for simultaneously dispensing a plurality of microliter sample quantities. To this end, in accordance with the principles of the present invention, there is provided a frame member for supporting a plurality of small capillary tubes and a slide member cooperating with and movably disposed with respect to the frame member for carrying a like plurality of thin wire elements. Each of the thin wire elements carried by the slide member is movably inserted inside a corresponding capillary tube to form a plurality of microliter dispensing elements. The capillary tubes are held in the frame member by easily removable flexible retainers so that each retainer may be replaced as it becomes worn. Also, due to the flexible nature of the retainers, each capillary tube may be removed from the dispenser without taking out the associated retainer. Moreover, due to the small size of each dispensing element, an effective liquidtight seal between each wire element and the inner wall of the corresponding capillary tube in which it is inserted may be provided by coating the wire element with a dense lubricant.

Accordingly, the primary object of the present invention is the provision of a multisample dispenser capable of simultaneously dispensing a plurality of microliter sample quantities.

Another object of the present invention is a simple but rugged dispenser formed from a minimum of components.

Another object is a multisample dispenser employing a plu rality of capillary tubes.

Another object is the provision of a multisample applicator including capillary tubes which are easily replaceable.

These and other objects and advantages of the present invention will become apparent from the following detailed description when read in conjunction with the accompanying drawings in which:

FIG. I is a partially exploded perspective view of the sample dispenser in accordance with the principles of the present invention; 1

FIG. 2 is a side view in section of the dispenser as assembled;

FIG. 3 is a front elevation view of the frame member;

FIG. 4 is a sectional view of the frame member taken along line 4-4 of the slide member illustrated in FIG. 1 showing in detail the overlap between the vertically extending holes in which the capillary tubes are inserted and the horizontally extending holes which contain the flexible retainers;

FIG. 5 is a sectional view of a portion of the assembled dispenser showing in detail the relationship between the flexible retainers and the capillary tubes.

With reference now to the drawings and more particularly to FIGS. 1 and 2 thereof, it will be observed that reference numeral l designates a T-shaped slide member including a pair of generally rectangular-shaped arms 1 and 2, which are LII disposed orthogonal to one another. The second arm 2 is rigidly secured to the front surface of the first arm 1 by means of a acrylic material, which in turn is bonded to the respective surfaces by a suitable adhesive such as methyl-methacrylade. A portion of the upper left-hand corner of the first arm I is cut out to form an abutting surface 9 whose function will be presently described. I

Equally spaced from one another along the top edge of the second arm 2 there is provided a plurality of small cylindrical holes 3, each of which is dimensioned to receive and hold one end of a thin needlelike wire plunger 7. A narrow flange 3, which includes a plurality of equally spaced vertically extending holes 5, projects outwardly from the bottom edge of the front surface of arm 2. As may be readily-seen from an inspection of the drawing, each of the holes 5 is located directly beneath or in line with one of the holes 3 and is dimensioned to receive one of the thin needlelike wire plungers 7. Each wire plunger 7 is firmly attached to support arm 2 by passing the plunger 7 through a hole 5 and bending one end to form a hook which is inserted into a corresponding support hole 3. Each hole 3 is then filled with a suitable adhesive to firmly retain the wire plunger 7.

The multisample applicator also includes a generally T- shaped frame member 12 comprising a guide arm 13 having a support arm 15 disposed orthogonal thereto. Like the first and second arms of the slide member 10, the guide and support arms 13 and 15, respectively, are rigidly fastened together by means of an acrylic material, which in turn is bonded to the respective surfaces by a suitable adhesive such as methylmethacrylade.

Guide arm 1 is provided with a generally rectangularshaped guide recess 14 in which the first arm 1 of slide member 10 is slidably retained. The sides of first arm 1 fit flush against the sides of recess 14 so that arm 1 may easily slide up and down in a vertical direction within recess 14.

Guide recess 14 includes a pair of narrow slots 20 and 22 (best shown in FIG. 3). As shown in FIG. 2, arm 1 of slide member 10 is held in recess 14 by a locking screw 30 which passes through slot 20 and has its threaded end inserted into an internally threaded bore 11 provided in slide member 10 at the junction point of arms 1 and 2. A flexible coiled spring 25 is suspended between a pin 26 provided at the top of slot 20 and the shaft of bolt 30 to bias the slide member 10 in an upward direction. The end of spring 25 fits around a small groove (not shown) formed in the shaft of bolt 30 to prevent the spring from latterly slipping along the shaft. The top portion of slot 20 is provided with a thin'backing or cover 21 to protect the spring 25 from inadvertent damage.

The extent of vertical travel of slide member 10 is governed by a bolt and nut combination 23 and 24 which combination is inserted through slot 22. That is, nut 24 is adapted to engage the abutting surface 9 of arm I. Consequently, by adjusting the position of nut 24 along slot 22 the extent of vertical travel of slide member 10 may be easily regulated. The end of pin 26 is flush with the side of slot 22 so as not to interfere with the adjusting of the bolt and nut combination.

A portion 16 of support member 15 is recessed to form a narrow flange 17 which has a plurality of vertically extending cylindrical holes 18 formed therein. Holes 18 are equally spaced along the back edge of flange l7 and each hole is dimensioned to receive a small capillary tube 19. Although in the exemplary embodiment eight capillary tubes are illustrated, it will be appreciated that any number of tubes may be used depending on the particular application. Typically, capillary tubes 19 are made of a glass and have a capacity of from approximately 1 microliter and up. Of course, it will be appreciated that the capacity of the capillary tube, as well as the diameter of the cooperating wire plunger employed are matters of choice. Moreover, the tubes may be made of any suitable plastic material if desired. i

As best shown in FIG. 5, each capillary tube 19 is firmly held within a hole 18 by means of a small flexible retainer 35, such as a generally circular rubber grommet, which is inserted into a similarly shaped horizontally extending hole 31 provided in flange 17. Each horizontally extending hole 31 overlaps or intersects a portion of vertically extending holes 18. That is, as may be clearly seen from FIG. 4, a portion 36 is common to both holes 18 and 31. Thus, when assembled, each flexible retainer 35 presses against the edge of a precision capillary tube 19 to firmly hold the capillary tube 19 in the hole 18. Of course, the extent of the overlap is such that the flexible retainer, although pressing firmly against the side of the capillary tube, does not deform the tube so as to obstruct or impede the free flow of liquid therethrough. When inserted through hole 18, the top portion of each capillary tube rests flush against the backing surface of recessed portion 16 to further aid in the rigidity of the tube once the apparatus is assembled.

A significant feature of the present invention lies in the easily replaceability of the precision capillary tubes 19. That is to say, as previously mentioned, each capillary tube 19 may be re moved by merely pulling out the tube with ones fingers. A new capillary tube may then be inserted into the hole 18 and firmly secured therein by the associated flexible retainer 35.

When completely assembled, all the capillary tubes 29 extend a like distance below the bottom of the support arm and above the flange 17. In addition, the location of each capillary tube 19 is such that it cooperates with a corresponding wire element or plunger 18 to form a plurality of microliter dispensers which may simultaneously dispense a plurality of samples of equal quantity. The wire elements 7 extend down inside the capillary tubes 19 and are simultaneously movable up and down in a vertical direction by moving slide member 10. A liquidtight seal is effected between each wire plunger 7 and the inside wall of each capillary tube 19 by coating each wire plunger with a highly dense lubricant, such as silicon grease. That is, due to the extremely small dimensions of the components the silicon grease effectively fills the annular space (about 0.001 inch) between the tube and the wire plunger to prevent inadvertent liquid leakage. This lubricant not only provides a liquidtight seal but, also, reduces the friction between the tube and the wire plunger to facilitate the movement of plungers 7. As an alternative or, in addition to the lubricant seal, the tip of each wire plunger may be Teflon coated to provide Teflon tipped plungers. Of course, it will be appreciated that in some applications the lubricant seal is not required.

In practice, the sample dispenser is loaded by first adjusting the slide-member 10 to set the wire elements 7 to a desired level within the capillary tubes 19 and then inserting the tubes into the liquid sample. The liquid is drawn into each tube 19 by the piston action of the wire plungers until all the tubes are filled. That is, the wire plungers are slowly withdrawn so the liquid flows into the tubes. The liquid samples are then expelled from the tubes by slowly depressing the slide member 10 which obviously causes the wire plungers 7 to force the liquid out of each capillary tube.

Numerous modifications and departures from the specific apparatus described herein may be made by those skilled in the art without departing from the inventive concept of the invention. For instance, alternate configurations other than the linear arrangement of the capillary tubes may be used. Thus, a plurality of capillary tubes may be arranged in a circular fashion on a cylindrical supporting member. Of course, this would necessitate a similar shaped slideable member carrying a like plurality of wire plungers arranged in a like fashion. In fact, a so-called seven point applicator formed by placing six capillary tubes in a circular fashion and one capillary tube at the center of the circle on a suitable cylindrical supporting member has been built and operates satisfactorily in practice. Moreover, instead of locating the flexible retainer elements tangentially to the capillary tubes, the rubber grommets may be inserted in the bottom of the vertically extending holes 18 and the capillary tubes inserted through the hole in each rubber grommet, in which case each tube would be held in its respective hole by the friction between the outside tube wall and the rubber grommet.

Iclaim:

l. A sample dispenser comprising a first member carrying at least one capillary tube, a second member movably disposed with respect to said first member and carrying at least one wire element, a portion of said wire element being movably inserted inside said capillary tube to form a dispensing element and said first member including resilient retaining means for firmly holding said capillary tube in said'first member, said latter means being easily removable from said first member to thereby permit the capillary tube to be removed.

2. A sample dispenser as defined in claim 1 wherein said wire element is coated with a relatively dense lubricant to provide an effective seal between the wire=element and the inner wall of the capillary tube in which it is disposed to prevent liquid leakage.

3. A multisample dispensing apparatus comprising a plurality of capillary tubes, a first member for holding said plurality of capillary tubes, a second member movably disposed with respect to said first member and carrying a plurality of wire elements, a portion of each of said wire elements being movably inserted inside a corresponding capillary tube to form a plurality of dispensing elements for simultaneously dispensing a plurality of predetermined sample quantities, and said first member including a plurality of resilient retaining means each of which firmly holds a capillary tube in said first member. I

4. A multisample dispensing apparatus as defined in claim 3 wherein each of said wire elements is coated with a relatively dense lubricant to provide a liquidtight seal between each wire element and the inner wall of the corresponding capillary tube in which the wire element is inserted.

5. A multisample dispensing apparatus comprising a plurality of capillary tubes, a first member comprising a pair of generally rectangular-shaped arms disposed orthogonal to each other, one of said arms including a guide recess and the other of said arms including a plurality of vertically extending holes each of which is dimensioned to receive an individual capillary tube and a plurality of horizontally extending holes each of which contains a similarly shaped easily removable retaining means, each of said horizontally extending holes intersecting said vertically extending holes so that each retaining means presses firmly against the side of a capillary tube to hold the capillary tube tightly within the vertically extending hole, and a second member movably disposed with respect to said first member and carrying a plurality of wire elements, a portion of each of said wire elements being movably inserted inside a corresponding capillary tube to form a plurality of dispensing elements for simultaneously dispensing a plurality of predetermined sample quantities.

6. A multisample dispensing apparatus as defined in claim 5 wherein said second member comprises a generally rectangular-shaped support arm and a generally rectangular-shaped slide arm disposed orthogonal to each other, said support arm carrying said plurality of wire elements and said slide arm being slidably disposed within said guide recess, and means to hold said first member within said guide recess.

7. A multisample applicator as defined in claim 6 comprising in addition a flexible bias means connected between said first member and said slide arm to bias said second member in an upward direction.

8. A multisample applicator as defined in claim 7 wherein each of said wire elements is coated with a relatively dense lubricant to provide an effective seal between each wire element and the inside wall of the capillary tube in which the wire element is inserted.

9. A multisample applicator as defined in claim 8 wherein the slide arm of said second member includes a cut out portion forming an abutting surface and said guide recess includes an adjustable stop means arranged to engage said abutting sur face to limit the extent of upward travel of said second member.

10. A sample dispenser as defined in claim 1 wherein said resilient retaining means comprises a flexible rubber grommet.

retaining means carried by said first member and cooperating with said capillary tube for firmly holding said capillary tube in said first member whereby said capillary tube may be easily removed from said first member. 

1. A sample dispenser comprising a first member carrying at least one capillary tube, a second member movably disposed with respect to said first member and carrying at least one wire element, a portion of said wire element being movably inserted inside said capillary tube to form a dispensing element and said first member including resilient retaining means for firmly holding said capillary tube in said first member, said latter means being easily removable from said first member to thereby permit the capillary tube to be removed.
 2. A sample dispenser as defined in claim 1 wherein said wire element is coated with a relatively dense lubricant to provide an effective seal between the wire element and the inner wall of the capillary tube in which it is disposed to prevent liquid leakage.
 3. A multisample dispensing apparatus comprising a plurality of capillary tubes, a first member for holding said plurality of capillary tubes, a second member movably disposed with respect to said first member and carrying a plurality of wire elements, a portion of each of said wire elements being movably inserted inside a corresponding capillary tube to form a plurality of dispensing elements for simultaneously dispensing a plurality of predetermined sample quantities, and said first member including a plurality of resilient retaining means each of which firmly holds a capillary tube in said first member.
 4. A multisample dispensing apparatus as defined in claim 3 wherein each of said wire elements is coated with a relatively dense lubricant to provide a liquidtight seal between each wire element and the inner wall of the corresponding capillary tube in which the wire element is inserted.
 5. A multisample dispensing apparatus comprising a plurality of capillary tubes, a first member comprising a pair of generally rectangular-shaped arms disposed orthogonal to each other, one of said arms including a guide recess and the other of said arms including a plurality of veRtically extending holes each of which is dimensioned to receive an individual capillary tube and a plurality of horizontally extending holes each of which contains a similarly shaped easily removable retaining means, each of said horizontally extending holes intersecting said vertically extending holes so that each retaining means presses firmly against the side of a capillary tube to hold the capillary tube tightly within the vertically extending hole, and a second member movably disposed with respect to said first member and carrying a plurality of wire elements, a portion of each of said wire elements being movably inserted inside a corresponding capillary tube to form a plurality of dispensing elements for simultaneously dispensing a plurality of predetermined sample quantities.
 6. A multisample dispensing apparatus as defined in claim 5 wherein said second member comprises a generally rectangular-shaped support arm and a generally rectangular-shaped slide arm disposed orthogonal to each other, said support arm carrying said plurality of wire elements and said slide arm being slidably disposed within said guide recess, and means to hold said first member within said guide recess.
 7. A multisample applicator as defined in claim 6 comprising in addition a flexible bias means connected between said first member and said slide arm to bias said second member in an upward direction.
 8. A multisample applicator as defined in claim 7 wherein each of said wire elements is coated with a relatively dense lubricant to provide an effective seal between each wire element and the inside wall of the capillary tube in which the wire element is inserted.
 9. A multisample applicator as defined in claim 8 wherein the slide arm of said second member includes a cut out portion forming an abutting surface and said guide recess includes an adjustable stop means arranged to engage said abutting surface to limit the extent of upward travel of said second member.
 10. A sample dispenser as defined in claim 1 wherein said resilient retaining means comprises a flexible rubber grommet.
 11. A sample dispenser comprising a capillary tube, a first member carrying said capillary tube, a wire element, a second member carrying said wire element, said second member being movably disposed with respect to said first member, a portion of said wire element being slidably inserted inside said capillary tube to form a dispensing element, and resilient retaining means carried by said first member and cooperating with said capillary tube for firmly holding said capillary tube in said first member whereby said capillary tube may be easily removed from said first member. 